This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The corpus luteum is a transient endocrine gland derived from the ovarian follicle after ovulation;this gland is the primary source of the steroid hormone progesterone, which is essential for the establishment and maintenance of intrauterine pregnancy in mammals. Therefore, knowledge of the processes controlling the functional lifespan of the corpus luteum is directly relevant to controlling fertility and treating certain types of infertility. Evidence suggests that the process called programmed cell death or apoptosis is associated with luteal regression in many species, but the regulation and molecular mechanisms occurring during luteal apoptosis are unknown. Accordingly, the specific aims of this project are: (1) To determine the changes in the pro-apoptotic genes (caspases -2, -3, -8, and -9) during the lifespan of rat corpus luteum in the estrous cycle and pregnancy;(2) To evaluate the regulation of these pro-apoptotic genes by the luteolytic hormone prostaglandin F2 alpha;and (3) To determine whether the anti-apoptotic agent sphingosine-1-phosphate (S1P) will prevent caspase activation and luteolysis of the corpus luteum. The results of the proposed studies will facilitate the design of critical comparative studies to determine the relevance of these apoptotic pathways to the primate CL, and ultimately, clinical syndromes of luteal dysfunction.